FIG 7 .

Modifications of host cell translation and stress response by DENV infection. Early in DENV infection, host cell translation is repressed. While assembly of the preinitiation complex and translation elongation remain unaffected, translation initiation is stalled after association of the 60S ribosomal subunit with cellular mRNA (monosomal RNA) (red blunted arrows). Interestingly, DENV infection activates the p38α-Mnk1 pathway, resulting in the phosphorylation of eIF4E (green arrows). While eIF4E phosphorylation does not account for DENV-induced translation repression, it might regulate the selective translation of specific mRNA subsets (green dashed arrow). DENV genome replication occurs through dsRNA intermediates that are sensed by PKR, leading to PKR autophosphorylation and activation (green arrow). However, the downstream phosphorylation of eIF2α, a direct target of the activated PKR, is inhibited as well as the assembly of both eIF2α-dependent and -independent SGs (red blunt-ended arrows). Altogether, during DENV infection translation suppression is uncoupled from the activation of the stress response.